Immunity in cutaneous leishmaniasis has been linked to the activities of parasite-specific T cells. Previous work by the applicant has shown that L3T4+ L. major-specific T cells can have an exacerbative effect on murine cutaneous leishmaniasis and that dampening the activities of these cells can convert a genetically-susceptible mouse into an animal that resolves its lesions, eliminates its parasite burden and becomes resistant to rechallenge. Taken collectively, these observations raise the question of whether immunity in cutaneous leishmaniasis is mediated by L3T4+ T cells acting in limited numbers or whether immunity is mediated by other T cell subsets such as Lyt-2+ T cells. This proposal will concentrate on determining the relative role of L3T4+ and Lyt-2+ parasite-specific T cells in immunity to cutaneous leishmaniasis in the mouse. It will do so by examining the effect of L3T4+ and Lyt-2+ parasite-specific T cells on cutaneous leishmaniasis in adoptive transfer studies using syngeneic recipients partially or fully depleted of T cells so as to control the participation of host T cells in the experiments and by assessing the presence of L3T4+ and Lyt-2+ parasite-specific T cells during the course of infection using assays for cell phenotype and function or using immunohistopathology. In addition, the proposal will examine the importance of macrophages in cutaneous leishmaniasis by assessing the number and nature (especially I-A-positivity) of macrophages in the lesion. It is felt that since the studies thus far have shown that certain parasite-specific T cell responses can be detrimental to the host, the results of the studies proposed here will be of fundamental importance to an understanding of immunity to leishmaniasis itself, and perhaps, to infectious disease in general. Moreover, understanding the basis of protective immunity in leishmaniasis should facilitate the development of a vaccine for the disease.